Isocyanide between alkyl

The valence-bond picture does not adequately express a difference between various isocyanides. There are interesting differences between alkyl and aryl isocyanides, discussed below. 

One additional point should be discussed here, concerning the substantial emphasis that has been placed on the differences between alkyl and aryl isocyanides. It has been suggested, primarily on the basis of infrared evidence, that aryl isocyanides are better 7r-acceptors than alkyl isocyanides (90). Qualitatively this difference is easily rationalized. One can see that delocalization of charge into 7r -orbitals on an aryl ring in aryl isocyanide-metal complexes should be possible, whereas no such possibility exists for alkyl isQcyanide-metal complexes this means that aryl isocyanides should be better ir-acceptors. Of course, the simple qualitative model gives one no measure of the relative importance of this effect. 

It has been reported that [1+ 4]-cycloaddition between alkyl isocyanides and 3-benzylidene-2,4-pentadione followed by tautomerisation of the resulting iminolac-tone gives the /V- a 1 k y 1 - 2 - a m i n o fu r a n s 71 (R = cyclohexyl, Bu, PhCH2) (Scheme 14) (97MC697). However, subsequent studies have shown that the isolated products are the pyrrol-2-ones 72, which are probably formed by oxidation of the intermediate 2-aminofurans 71 (04TL1413) (see also Section Il.C.l.a). 

Other isocyanate syntheses that have recently been reported include several well-known reactions. One area which has attracted considerable attention is that of the direct production of isocyanates by the carbonylation of nitro-arenes. Both mono- and di-isocyanates are claimed to have been produced using various catalysts palladium, rhodium, and iron compounds often being cited. Other preparative reactions for isocyanates which have appeared in the literature include the acid catalysed hydrolysis of isocyanide dihalides and the reaction between alkyl halides and alkali-metal cyanates, although the latter has been given a modern flavour by the use of a polymer-supported reagent. ... 

M. Quai, S. Prattini, U. Vendrame, M. Mondoni, S. Dossena, E. Cereda, Tetrahedron Lett. 2004, 45, 1413-1416. 5-Hydroxy-27f-pyrrol-2-ones and not 2-aminofurans are the cycloaddition products between alkyl isocyanides and benzyliden-1,3-diketones. 

More important than this, however, is the fact that until recently there have been no substantial differences observed in the chemistry of metal complexes of alkyl and aryl isocyanides. In general, the choice of which isocyanide to use seems to be made largely at random, dictated perhaps by convenience as much as any other factor. Lacking any substantial chemical differences between the two groups of complexes, one might wish to minimize, rather than emphasize, this comparison. However, several observations have recently been made which seem to substantiate the earlier conclusion. 

Liquid crystals based on aliphatic isocyanides and aromatic alkynyls (compounds 16) show enantiotropic nematic phases between 110 and 160 °C. Important reductions in the transition temperatures, mainly in clearing points (<100 °C), areobtained when a branched octyl isocyanide is used. The nematic phase stability is also reduced and the complexes are thermally more stable than derivatives of aliphatic alkynes. Other structural variations such as the introduction of a lateral chlorine atom on one ring of the phenyl benzoate moiety or the use of a branched terminal alkyl chain produce a decrease of the transition temperatures enhancing the formation of enantiotropic nematic phases without decomposition. 

Comparison between the half-wave potentials (equations 2 to 4) of [Cr(CNR)6](PF6)2, e.g. for R = Bu , -1.04, -0.28 and 0.84 V (versus SCE),22 with those for [Cr(CNPh)6](PF6)2, i.e. -0.35, 0.25 and 1.00 V,20 shows that alkyl and aryl isocyanides favour respectively the higher and the lower oxidation states as expected from the greater a-donor and weaker jr-acceptor capabilities of the alkyl over the aryl isocyanides. Similarly, the phosphines in the mixed ligand complexes (Table 3), 23 relative to isocyanide ligands, stabilize the Cr111 oxidation state. The great difference in the relative stabilities of Cr—C bonds in the cyano and phenyl isocyanide complexes is indicated by the magnitude of the shift (ca. 2.0 V) between the Cr(CN) "/Cr(CN)r (-1.130 V) and the Cr(CNPh)i+/Cr(CNPh)i+ reduction potentials.28... 

The rotation of alkyl and aryl substituents about the N-R single bond may be severely restricted on steric grounds in most polyisocyanides, (which usually contain branching at the a-carbon of substituent R). This is consistent with the observation that the NMR spectrum of whole samples of J-poly(a-phenylethyl isocyanide) in tetrachloroethylene undergoes little change upon heating between room temperature and 128° C (4). 

The generally accepted valence bond and molecular orbital (MO) approach to the bonding of metal isocyanides has been well described in Treichel s review (6), and has been used to rationalize (i) variations in IR stretching frequencies between bonded and nonbonded isocyanides, and (ii) the better Tt-acceptor qualities of aryl versus alkyl isocyanide groups (53,54). In valence bond theory the canonical forms involved in metal isocyanide bonds are... 

It is interesting that aldol-type condensation of tosylmethyl isocyanide (16) with aldehydes is catalyzed by the silver catalyst more stereoselectively than that catalyzed by the gold catalyst under the standard reaction conditions (Scheme 8B1.9) [26], Elucidation of the mechanistic differences between the gold and silver catalysts in the asymmetric aldol reaction of 16 needs further study. Oxazoline 17 can be converted to optically active a-alkyl-p-(A-methyl-amino)ethanols. 

The Passerini reaction between a-chloroketones, isocyanides, and carboxylic acids afforded a-acyloxy-jS-chlorocarboxamides 52, which, on treatment with an excess of powdered KOH in tetrahydrofuran, underwent O-deacylation followed by a Darzens-type O-alkylation to give the functionalized oxiranes 53. When carboxamides 52 were treated with an excess of CsF, with or without a phase-transfer catalyst, a different ring closure took place to afford 3-acyloxy-2-azetidinones 54 in high yields (Scheme 2.21) [46]. 

A less common approach to 2,5-diketopiperazine was reported by Marcaccini et al. [79] who used a Ugi-4CR between amines, aldehydes, isocyanides, and chloroacetic acid to get adducts 140. Treatment of 140 with ethanolic potassium hydroxide led to an intramolecular amide N-alkylation reaction, giving 2,5-diketopiperazines 141... 

The Passerini-3CR between bifunctional 6-oxo-4-thiacarboxylic acids and alkyl-isocyanides, in the presence of a catalytic amount of tributylamine, afforded the tetracyclic structure 171, which included the 1,4-benzothioxepin group and an unexpected oxazolidinone ring, with formation of a rare orthoamide group (Scheme 2.62) [94]. 

Early findings by Suzuki and co-workers [109] showed that the palladium-catalyzed iminocarbonylative cross-coupling reaction between 9-alkyl-9-BBN derivatives, t-butylisocyanide, and arylhalides gives access to alkyl aryl ketones 132 after hydrolysis of the corresponding ketimine intermediates 131. Presumably, the concentration of free isocyanide is kept to a minimum by its coordination with the borane. Formation of an iminoacylpalladium(II) halide 130 by insertion of isocyanide to the newly formed arylpalladium complex followed by a transmetallation step afford the ketimine intermediates 131 (Scheme 8.52). 

In the uncondensed imidazoles the standard method reacts an a-aminocarbonyl compound with a thiocyanate (see Section 4.1 and Table 4.1.1). If a 2-alkylthioimidazole is required directly, one can combine an N-alkyT or A -arylcarbonimidodithioate in refluxing acetic acid with the aminocarbonyl substrate (see Section 4.1 and Scheme 4.1.3). Alternatively, reaction between thiourea and a two-carbon synthon (ot-hydroxy-, a-halogeno-, a-dicarbonyl) leads to imidazoline-2-thiones (see Section 4.3). In sulfuric acid, 3-butynylthiourea cyclizes to 4,5-dimethylimidazolin-2-thione (see Section 2.2.1). 1-Substituted 2-methylthioimidazoles can be made, albeit in rather poor yields, from appropriately substituted 2-azabutadienes (see Section 3.2 and Scheme 3.2.3), and 2-arylthioimidazoles are available in moderate yields from benzyl isocyanides and arylsulfenyl chlorides (see Section 4.2 and Scheme 4.2.12). Ring transformations of 5-amino-2-alkylaminothiazoles and 2-acylamino-5-aminothiazoles may have occasional applications (see Section 6.1.2.7). The ease with which a thiol group or imidazole or benzimidazole can be alkylated, in comparison with the annular nitrogens, usually makes it more convenient to prepare alkylthioimidazoles from the thiols (or thiones). 

Arylthioimidazoles can be made in high yields when thiophenates react with At-(l-cyanoalkyl) alkylidene A -oxides. Alkyl and aralkyl thiolates, however, react much less readily (see Section 2.1.1 and Scheme 2.1.10). Imidazole-4-thioethers can be made in a general reaction between nitriles and a range of isocyanides which are susceptible to o -metallation (see Section 4.2, Scheme 4.2.2 and Table 4.2.1). Oxoketene acetals bearing alkylthio substituents react with nitrosoaromatics to give 5-acyl-4-alkylthio-l-arylimidazoles in moderate to good yields (see Section 3.2 and Scheme 3.2.5). 

The nitrogen atom in a-ferrocenylalkylamines generally shows the same reaction pattern as that in other amines alkylation and acylation do not provide synthetic problems. Due to the high stability of the a-ferrocenylalkyl carbocations, ammonium salts readily lose amine and are, therefore, important synthetic intermediates. Acylation of primary amines with esters of formic acid gives the formamides, which can be dehydrated to isocyanides by the standard POClj/diisopropylamine technique (Fig. 4-16) [92]. Chiral isocyanides are obtained from chiral amines without any racemization during the reaction sequence. The isocyanides undergo normal a-addition at the isocyanide carbon, but could not be deprotonated at the a-carbon by even strong bases. This deviation from the normal reactivity of isocyanides prompted us to study the electrochemistry of these compounds, but no abnormal redox behaviour, compared with that of other ferrocene derivatives, was detected [93]. The isocyanides form chromium pentacarbonyl complexes on treatment with Cr(CO)s(THF) (Fig. 4-16) and electrochemistry demonstrated that there is no electronic interaction between the two metal centres. 

Polymerization of isocyanides is a thermodynamically feasible process, in agreement with the stoichiometric multiple insertion observed in reactions between metal-alkyl complexes and isocyanides. The entropy loss in the case of isocyanides is lower than for insertion of CO. Isocyanide insertions into palladium-alkyl a bonds are faster than those for the platinum(II) analogues. The latter, on the other hand, usually lead to more stable and better defined products. Insertion of isocyanides into platinum-carbon bonds has been studied extensively Reaction (j) is typical the ionic product was strongly suggested by observation that the compounds isolated under mild conditions are 1 1 electrolytes. 

A review of lone pair effects involving multiple bonds between heavier main group elements contains much of relevance to pj -bonded phosphorus systems. The diphosphene (295) has been shown to undergo cycloaddition reactions with isocyanides, to give the iminodiphosphiranes (296)." A thirtyfive-fold excess of methyl triflate is needed to convert the diphosphene (297) to the salt (298), which is unstable in non-polar solvents. Experimental data show that the P=P bond becomes stronger on alkylation as is the case for N=N compounds. 

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